The present invention relates to the field of respiratory therapy and specifically to the field of treating Chronic Obstructive Pulmonary Disease (COPD).
COPD is a worldwide problem of high prevalence, effecting tens of millions of people and is one of the top five leading causes of death. COPD is a spectrum of problems, including bronchitis and emphysema, and involves airway obstruction, tissue elasticity loss and trapping of stagnant CO2-rich air in the lung. There are two basic origins of emphysema; a lesser common origin stemming from a genetic deficiency of alpha1-antitripsin and a more common origin caused by toxins from smoking or other environment sources. In both forms there is a breakdown in the elasticity in the functional units, or lobules, of the lung changing clusters of individual alveoli into large air pockets, thereby significantly reducing the surface area for gas transfer. In some cases air leaks out of the frail lobules to the periphery of the lung causing the lung's membranous lining to separate from the parenchymal tissue to form large air vesicles called bullae. The elasticity loss also causes small airways to become flaccid tending to collapse during exhalation, trapping large volumes of air in the now enlarged air pockets, thus reducing bulk air flow exchange and causing CO2 retention in the trapped air. Mechanically, because of the large amount of trapped air in the lung at the end of exhalation, known as elevated residual volume, the intercostal and diaphragmatic inspiratory muscles are forced into a pre-loaded condition, reducing their leverage at the onset of an inspiratory effort thus increasing work-of-breathing and causing dyspnea. In emphysema therefore more effort is expended to inspire less air and the air that is inspired contributes less to gas exchange.
Conventionally prescribed therapies for emphysema and other forms of COPD include pharmacological agents such as aerosolized bronchodilators and anti-inflammatories; long term oxygen therapy (LTOT); respiratory muscle rehabilitation; pulmonary hygiene such as lavage or percussion therapy; continuous positive airway pressure (CPAP) via nasal mask; trans-tracheal oxygen therapy (TTOT) via tracheotomy. These therapies all have certain disadvantages and limitations with regard to effectiveness because they do not address, treat or improve the debilitating elevated residual volume in the lung. After progressive decline in lung function despite attempts at conventional therapy, patients may require mechanical ventilation.
Newer mechanical ventilation techniques to address COPD is well reported in the literature and include HeliOx ventilation, Nitric Oxide ventilation, liquid ventilation, high frequency jet ventilation, and tracheal gas insufflation. Because these modes do nothing to address, treat or improve the hyperinflated residual volume of the COPD or emphysema patient, and because mechanical ventilation is performed on the lung as a whole and inherently can not target a specific lung area that might be more in need of treatment, mechanical ventilation is an ineffective solutions.
There have been significant efforts to discover new treatments such as treatment with substances that protect the elastic fibers of the lung tissue. This approach may slow the progression of the disease by blocking continued elastin destruction, but a successful treatment is many years away, if ever. It may be possible to treat or even prevent emphysema using biotechnology approaches such as monoclonal antibodies, stem cell therapy, viral therapy, cloning, or xenographs however, these approaches are in very early stages of research, and will take many years before their viability is even known.
In order to satisfy the more immediate need for a better therapy a surgical approach called lung volume reduction surgery (LVRS) has been extensively studied and proposed by many as a standard of therapy. This surgery involves surgically resecting some of the diseased hyperinflated lung tissue, usually the lung's apical sections, thus reducing residual volume and improving the patient's breathing mechanics and possibly gas exchange. Approximately 9000 people have undergone LVRS, however the results are not always favorable. There is a high complication rate of about 20%, patients don't always feel a benefit possibly due to the indiscriminate selection of tissue being resected, there is a high degree of surgical trauma, and it is difficult to predict which patients will feel a benefit. Therefore LVRS is not a practical solution and inarguably some other approach is needed. The attention on LVRS has created some new ideas on non-surgical approaches to lung volume reduction. These approaches are presently in experimental phases and are reviewed below.
New minimally invasive lung volume reduction methods described in the prior art includes U.S. Pat. Nos. 5,972,026; 6,083,255; 6,174,323; 6,488,673; 6,514,290; 6,287,290; 6,527,761; 6,258,100; 6,293,951; 6,328,689; 6,402,754; 0020042564; 0020042565; 0020111620; 0010051799; 0020165618; and foreign patents EP1078601; WO98/44854; WO99/01076; WO99/32040; WO99/34741; WO99/64109; WO0051510; WO00/62699; WO01/03642; WO01/10314; WO01/13839; WO01/13908 WO01/66190.
Patent # 6328689 describes a method wherein lung tissue is sucked and compressed into a compliant sleeve placed into the pleural cavity through an opening in the chest. While this method may be less traumatic than LVRS it presents new problems. First, it will be difficult to isolate a bronchopulmonary segment for suction into the sleeve. In a diseased lung the normally occurring fissures that separate lung segments are barely present. Therefore, in order to suck tissue into the sleeve as proposed in the referenced invention, the shear forces on the tissue will cause tearing, air leaks and hemorrhage. Secondly the compliant sleeve will not be able to conform well enough to the contours of the chest wall therefore abrading the pleural lining as the lung moves during the breathing, thus leading to other complications such as adhesions and pleural infections.
U.S. Patent applications 2002/0147462 and 2001/0051799 explain methods wherein adherent substances are introduced to seal the bronchial lumen leading to a diseased area. It is proposed in these inventions that the trapped gas will dissipate with time. The main flaw with this method is that trapped gas will not effectively dissipate, even given weeks or months. Rather, a substantial amount of trapped gas will remain in the blocked area and the area will be at heightened infection risk due to mucus build up and migration of aerobic bacteria. Gas will not dissipate because: (1) blood perfusion is severely compromised, exacerbated by the Euler reflex, hence reducing gas exchange; (2) the tissue has low diffusivity for CO2; and (3) additional gas will enter the blocked area through intersegmental collateral flow channels from neighboring areas. Another disadvantage with this invention is adhesive delivery difficulty; Controlling adhesive flow along with gravitational effects make delivery awkward and inaccurate. Further, if the adhesive is too hard it will be a tissue irritant and if the adhesive is too soft it will likely lack durability and adhesion strength. Some inventors are trying to overcome these challenges by incorporating biological response modifiers to promote tissue in-growth into the plug, however due to biological variability these systems will be unpredictable and will not reliably achieve the relatively high adhesion strength required. A further disadvantage with an adhesive bronchial plug, assuming adequate adhesion, is removal difficulty, which is extremely important in the event of post obstructive pneumonia unresponsive to antibiotic therapy, which is likely to occur as previously described.
U.S. Pat. No. 5,972,026 describes a method wherein the tissue in a diseased lung area is shrunk by heating the collagen in the tissue. The heated collagen fibers shrink in response to the heat and then reconstitute in their shrunk state. However, a flaw with this method is that the collagen will have a tendency to gradually return towards its initial state rendering the technique ineffective.
U.S. Pat. Nos. 6,174,323 and 6,514,290 describe methods wherein the lung tissue is endobronchially retracted by placing anchors connected by a cord at distal and proximal locations then shortening the distance between the anchors, thus compressing the tissue and reducing the volume of the targeted area. While technically sound, there are three fundamental physiological problems with this method. First, the rapid mechanical retraction and collapse of the lung tissue will cause excessive shear forces, especially in cases with pleural adhesions, likely leading to tearing, leaks and possibly hemorrhage. Secondly, distal air sacs remain engorged with CO2 hence occupy valuable space without contributing to gas exchange. Third, the method does not remove trapped air in bullae. Also, the anchors described in the invention are not easily removable and they will likely tear the diseased and fragile tissue.
U.S. Patent Applications 2002/0042564, 2002/0042565 and 2002/0111620 describe methods where artificial channels are drilled in the lung parenchyma so that trapped air can then communicate more easily with the conducting airways and ultimately the upper airways, and/or to make intersegmental collateral channels less resistive to flow, so that CO2-rich air can be expelled better during respiration. Its inventors propose that this method may be effective in treating homogeneously diffuse emphysema by preventing air trapping throughout the lung, however the method does not appear to be feasible because of the vast number of artificial channels that would need to be created to achieve effective communication with the vast number lobules trapping gas.
U.S. Pat. Nos. 6,293,951 and foreign patent WO01/66190 describe placing a one-way valve in the feeding bronchus of the diseased lung area. The proposed valves are intended to allow flow in the exhaled direction but not in the inhaled direction, with the intent that over many breath cycles, the trapped gas in the targeted area will escape through the valve thus deflating the lung compartment. This mechanism can be only partially effective due to fundamental lung mechanics, anatomy and physiology. First, because of the low tissue elasticity of the targeted diseased area, a pressure equilibrium is reached soon after the bronchus is valved, leaving a relatively high volume of gas in the area. Hence during exhalation there is an inadequate pressure gradient to force gas proximally through the valve. Secondly, small distal airways still collapse during exhalation, thus still trapping air. Also, the area will be replenished with gas from neighboring areas through intersegmental channels, trapped residual CO2-rich gas will not completely absorb or dissipate over time and post-obstructive pneumonia problems will occur as previously described. Finally, a significant complication with a bronchial one-way valve is inevitable mucus build up on the proximal surface of the valve rendering the valve mechanism faulty.
U.S. Pat. Nos. 6,287,290 and 6,527,761 describe methods for deflating a diseased lung area by first isolating the area from the rest of the lung, then aspirating trapped air by applying vacuum to the bronchi in the area, and plugging the bronchus either before or after deflation. These methods also describe the adjunctive installation of Low Molecular Weight gas into the targeted area to facilitate aspiration and absorption of un-aspirated volume. It is appreciated in these inventions that the trapped air in the lung is not easily removable, and that aspiration of the trapped air may require sophisticated vacuum control. While apparently technically, physiologically and clinically sound, these methods still have some inherent and significant disadvantages. First, aspiration of trapped air by negative pressure is extremely difficult and sometimes impossible because mucus in the distal airways will instantly plug the airways when vacuum is applied because of the vacuum-induced constriction of the fragile airways. Also, it is difficult to avoid collapse of the distal airways when they are exposed to vacuum due to their diseased in-elastic state. Special vacuum parameters may enhance aspiration effectiveness by attempting to mitigate airway collapse, but the parameters will likely be different for different lung areas, for different times and for different patients because effective vacuum parameters will depend on the condition of hundreds of minute airways communicating with the trapped gas. These airways, although theoretically in parallel with one another, empirically do not behave in unison as one collective airway, but rather as many individual dynamic systems. Therefore, aspiration of an effective volume of trapped air using vacuum may be impractical to implement. Secondly, a vacuum technique will not remove the excessively trapped air in bullae. Third, the collapse-by-aspiration techniques described in these patents explain a relatively rapid deflation of the targeted area conducted while a clinician is attending to the instruments introduced into the lung, for example generally less than thirty minutes, which is the time a patient can tolerate the bronchoscopic procedure. Collapse-by-aspiration in this short a time period will often produce traumatic tissue shearing between the collapsing and non-collapsing areas, leading to tearing, leaks and hemorrhage, especially if there are adhesions and bullae present. Forth, although installation of low molecular weight gas may facilitate collapse by absorption, infusion of respiratory gases from neighboring lung areas through intersegmental collateral channels will refill the targeted lung area rending collapse incomplete. Some additional disadvantages of this technique include post-obstructive pneumonia, assuming incomplete air removal; the technique requires constant attendance of clinician which is impractical if a slow, gradual collapse of the lung area is desired; and finally the technique will be limited to large lung sections because suctioning requires a relatively large catheter inner diameter in order to avoid mucus plugging of the instruments.
To summarize, methods for minimally invasive lung volume reduction are either ineffective in collapsing the hyperinflated lung areas, or do not remove air in bullae, or collapse tissue too rapidly causing shear-related injury, or cause post-obstructive pneumonia.
The present invention disclosed herein takes into consideration the problems and challenges not solved by the aforementioned prior art methods in treating COPD and emphysema. In summary, this invention accomplishes (1) effective collapse of the targeted bronchopulmonary compartment including bullae by keeping the airways of the targeted area open by applying positive pressure to them and employing gas diffusion laws, (2) a gradual controlled atraumatic collapse of the targeted bronchopulmonary compartment thus avoiding the shearing issues associated with attempted rapid collapse, (3) avoidance of re-inflation by gas inflow through collateral channels using pressure gradients and gas diffusion laws, and (4) avoidance of post obstructive pneumonia. These methods and devices thereof are described below in more detail.